HPSEC法检测头孢孟多酯钠中聚合物含量并考察辅料对聚合物产生的影响  

Determination of Polymers in Cefamandole Sodium by HPSEC and Effects of Pharmaceutical Excipients on Producing of Polymers

作　　者：孙青 张彤 金艳 蒋惠源 Sun Qing;Zhang Tong;Jin Yan;Jiang Huiyuan(Management Committee of Taizhou Pharmaceutical High-tech Industrial Park,Jiangsu Taizhou 225300,China;Taizhou Drug Inspection Institute of Jiangsu Province)

机构地区：[1]泰州医药高新技术产业园区管理委员会,江苏泰州225300 [2]泰州市药品检验院

出　　处：《中国药师》2021年第6期1175-1181,共7页China Pharmacist

摘　　要：目的:建立高效分子排阻色谱(HPSEC)法测定头孢孟多酯钠中聚合物的含量,用液相色谱-串联质谱法对头孢孟多酯钠聚合物进行确证,并考察辅料碳酸钠添加量对聚合物产生的影响。方法:采用TSK gel G2000SWXL凝胶色谱柱(30 cm×7.8 mm,5μm);检测波长:270 nm;流动相:0.0005 mol·L^(-1)乙酸铵溶液(用氨水调至pH 7.0)-乙腈(95∶5);流速:0.6 ml·min^(-1);柱温:25℃;进样体积:10μl。离子源:电喷雾离子(ESI)源;毛细管电压:2.5 k V;离子源温度:120℃;脱溶剂气温度:500℃;脱溶剂气流速:800 L·h^(-1);锥孔电压:25 V。结果:头孢孟多酯钠主峰前的杂质峰为聚合物,能与主峰有效分离;主峰的线性范围为0.203~1013.000μg·ml^(-1)(r=0.9998),检测限为0.101μg·ml^(-1),定量限为0.302μg·ml^(-1),精密度良好。头孢孟多酯钠溶液稳定性较差,溶液放置超过12 h,产生聚合物的速度明显加快;在头孢孟多酯钠中添加20~60 mg·g^(-1)碳酸钠,聚合物含量的增长速度和主成分峰面积的下降速度都明显降低。结论:所建方法专属性强、耐用性好,灵敏度高,适用于头孢孟多酯钠中聚合物的测定;辅料碳酸钠添加量在20~60 mg·g^(-1)的范围内,有利于主成分头孢孟多酯的稳定,并能减少聚合物的产生。Objective:To establish a high performance size exclusion chromatography(HPSEC)method for the determination of polymers in cefamandole sodium,confirm the structures of polymers in cefamandole sodium by liquid chromatography-mass spectrometry,and analyze the effects of sodium carbonate additions on producing of polymers.Methods:The chromatographic column was a TSK gel G2000SWXL(30 cm×7.8 mm,5μm).The detection wavelength was 270 nm with the column temperature at 25℃.The mobile phase was 0.0005 mol·L^(-1) ammonium acetate solution(adjusting p H to 7.0 with ammonia)-methanol(95∶5)at a flow rate of 0.6 ml·min^(-1).The injection volume was 10μl.The ion source was an electrospray ion(ESI)source;the capillary voltage was 2.5 k V;the ion source temperature was at 120℃;the desolvent gas temperature was at 500℃;the desolvent gas flow rate was 800 L·h^(-1);the cone voltage was 25 V.Results:The impurity peaks before the main peak of cefamandole sodium were the peaks of polymers,and they could be separated effectively from the main peak.The linear range of the main drug was 0.203-1013.000μg·ml^(-1),the detection limit was 0.101μg·ml^(-1),the limit of quantification was 0.302μg·ml^(-1) and the method had good precision.The solution stability of cefamandole sodium was poor.If the solution was placed for more than 12 hours,the rate of polymer production was significantly increased.If adding 20-60 mg·g^(-1) sodium carbonate to the solution of cefamandole sodium,both the increase rate of polymer concentration and the decrease rate of main peak area were significantly reduced.Conclusion:HPSEC method has strong specificity,good durability and high sensitivity,which is suitable for the determination of polymers in cefamandole sodium.Addition quantity of pharmaceutical excipient sodium carbonate should be within the range of 20-60 mg·g^(-1),which is beneficial to the stability of cefamandole sodium and can reduce the production of polymers.

关 键 词：高效分子排阻色谱法 头孢孟多酯钠 聚合物 碳酸钠 

分 类 号：R917[医药卫生—药物分析学]